Summary Document Research on RDS Anti-addiction Modeling: Annotated Bibliography.

Annotated bibliography of genetic addiction risk severity (GARS) publications, pro-dopamine regulation in nutraceuticals (KB220 nutraceutical variants), and policy documents. Further research is required to encourage the field to consider "Reward Deficiency Syndrome (RDS) Anti-addiction Modeling" which involves early risk identification by means of genetic assessment similar to GARS, followed by induction of dopamine homeostasis by means of genetically guided pro-dopamine regulation similar to KB220. These results suggest that genetically based treatments may be a missing piece in the treatment of substance use disorder (SUD).

Addressing cortex dysregulation in youth through brain health check coaching and prophylactic brain development.

The Carter Center has estimated that the addiction crisis in the United States (US), if continues to worsen at the same rate, may cost the country approximately 16 trillion dollars by 2030. In recent years, the well-being of youth has been compromised by not only the coronavirus disease 2019 pandemic but also the alarming global opioid crisis, particularly in the US. Each year, deadly opioid drugs claim hundreds of thousands of lives, contributing to an ever-rising death toll. In addition, maternal usage of opioids and other drugs during pregnancy could compromise the neurodevelopment of children. A high rate of DNA polymorphic antecedents compounds the occurrence of epigenetic insults involving methylation of specific essential genes related to normal brain function. These genetic antecedent insults affect healthy DNA and mRNA transcription, leading to a loss of proteins required for normal brain development and function in youth. Myelination in the frontal cortex, a process known to extend until the late 20s, delays the development of proficient executive function and decision-making abilities. Understanding this delay in brain development, along with the presence of potential high-risk antecedent polymorphic variants or alleles and generational epigenetics, provides a clear rationale for embracing the Brain Research Commission's suggestion to mimic fitness programs with an adaptable brain health check (BHC). Implementing the BHC within the educational systems in the US and other countries could serve as an effective initiative for proactive therapies aimed at reducing juvenile mental health problems and eventually criminal activities, addiction, and other behaviors associated with reward deficiency syndrome.

Identification of stress-induced epigenetic methylation onto dopamine D2 gene and neurological and behavioral consequences.

The D2 dopamine receptor (DRD2) gene has garnered substantial attention as one of the most extensively studied genes across various neuropsychiatric disorders. Since its initial association with severe alcoholism in 1990, particularly through the identification of the DRD2 Taq A1 allele, numerous international investigations have been conducted to elucidate its role in different conditions. As of February 22, 2024, there are 5485 articles focusing on the DRD2 gene listed in PUBMED. There have been 120 meta-analyses with mixed results. In our opinion, the primary cause of negative reports regarding the association of various DRD2 gene polymorphisms is the inadequate screening of controls, not adequately eliminating many hidden reward deficiency syndrome behaviors. Moreover, pleiotropic effects of DRD2 variants have been identified in neuropsychologic, neurophysiologic, stress response, social stress defeat, maternal deprivation, and gambling disorder, with epigenetic DNA methylation and histone post-translational negative methylation identified as discussed in this article. There are 70 articles listed in PUBMED for DNA methylation and 20 articles listed for histone methylation as of October 19, 2022. For this commentary, we did not denote DNA and/or histone methylation; instead, we provided a brief summary based on behavioral effects. Based on the fact that Blum and Noble characterized the DRD2 Taq A1 allele as a generalized reward gene and not necessarily specific alcoholism, it now behooves the field to find ways to either use effector moieties to edit the neuroepigenetic insults or possibly harness the idea of potentially removing negative mRNA-reduced expression by inducing "dopamine homeostasis."

Noninvasive Surrogate for Physiologic Dead Space Using the Carbon Dioxide Ventilatory Equivalent: Testing in a Single-Center Cohort, 2017-2023.

OBJECTIVES: We sought to evaluate the association between the carbon dioxide (co2) ventilatory equivalent (VEqco2 = minute ventilation/volume of co2 produced per min), a marker of dead space that does not require a blood gas measurement, and mortality risk. We compared the strength of this association to that of physiologic dead space fraction (VD/Vt = [Paco2-mixed-expired Pco2]/Paco2) as well as to other commonly used markers of dead space (i.e., the end-tidal alveolar dead space fraction [AVDSf = (Paco2-end-tidal Pco2)/Paco2], and ventilatory ratio [VR = (minute ventilation × Paco2)/(age-adjusted predicted minute ventilation × 37.5)]). DESIGN: Retrospective cohort data, 2017-2023. SETTING: Quaternary PICU. PATIENTS: One hundred thirty-one children with acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All dead space markers were calculated at the same 1-minute timepoint for each patient within the first 72 hours of using invasive mechanical ventilation. The 131 children had a median (interquartile range, IQR) age of 5.8 (IQR 1.4, 12.6) years, oxygenation index (OI) of 7.5 (IQR 4.6, 14.3), VD/Vt of 0.47 (IQR 0.38, 0.61), and mortality was 17.6% (23/131). Higher VEqco2 (p = 0.003), VD/Vt (p = 0.002), and VR (p = 0.013) were all associated with greater odds of mortality in multivariable models adjusting for OI, immunosuppressive comorbidity, and overall severity of illness. We failed to identify an association between AVDSf and mortality in the multivariable modeling. Similarly, we also failed to identify an association between OI and mortality after controlling for any dead space marker in the modeling. For the 28-day ventilator-free days outcome, we failed to identify an association between VD/Vt and the dead space markers in multivariable modeling, although OI was significant. CONCLUSIONS: VEqco2 performs similarly to VD/Vt and other surrogate dead space markers, is independently associated with mortality risk, and may be a reasonable noninvasive surrogate for VD/Vt.

Vitamin B12 Supplementation in Psychiatric Practice.

PURPOSE OF REVIEW: Vitamin B12 (B12, cobalamin) deficiency has been associated with neuropsychiatric symptoms, suggesting a role for B12 supplementation both as a treatment for psychiatric symptoms due to B12 deficiency and as an augmentation strategy for pharmacological treatments of psychiatric disorders. This critical review discusses the major causes of B12 deficiency, the range of psychiatric and non-psychiatric manifestations of B12 deficiency, the indications for testing B12 levels, and the evidence for B12 supplementation for major psychiatric disorders. RECENT FINDINGS: We find that high-quality evidence shows no benefit to routine B12 supplementation for mild depressive symptoms or to prevent depression. There is very limited evidence on the role of B12 supplementation to augment antidepressants. No high-quality evidence to date suggests a role for routine B12 supplementation in any other major psychiatric disorder. No formal guidelines indicate when clinicians should test B12 levels for common psychiatric symptoms, in the absence of major risk factors for deficiency or cardinal symptoms of deficiency. No robust evidence currently supports routine B12 supplementation for major psychiatric disorders. However, psychiatrists should be aware of the important risk factors for B12 deficiency and should be able to identify symptoms of B12 deficiency, which requires prompt testing, medical workup, and treatment. Testing for B12 deficiency should be considered for atypical or severe psychiatric presentations.

First international consensus statement on sports psychiatry.

Sports psychiatry is a young field of medicine and psychiatry that focuses on mental health among athletes, and sports and exercise within psychiatry and mental disorders. However, the development of sports psychiatry and its fields of activity vary from region to region and are not uniform yet. Sports psychiatry and the role of sports psychiatrists have also already been discussed in the field of sports and exercise medicine, and within medical teams in competitive and elite sports. A uniform definition on sports psychiatry, its fields of activity, sports psychiatrist, and the essential knowledge, skills, and abilities (plus attitudes, eKSA+A) of the sports psychiatrist were developed as part of an International Society for Sports Psychiatry (ISSP) Summit, as well as First International Consensus Statement on Sports Psychiatry. Three fields of activity can be distinguished within sports psychiatry: (i) mental health and disorders in competitive and elite sports, (ii) sports and exercise in prevention of and treatment for mental disorders, and (iii) mental health and sport-specific mental disorders in recreational sports. Each of these fields have its own eKSA+A. The definitions on sports psychiatry and sports psychiatrists, as well as the framework of eKSA+A in the different fields of activity of sports psychiatrists will help to unify and standardize the future development of sports psychiatry, establish a standard of service within sports psychiatry and together with the neighboring disciplines, and should be included into current, and future sports psychiatry education and training.

Red blood cell transfusion-related dynamics of extracellular vesicles in intensive care patients: a prospective subanalysis.

Extracellular vesicles (EVs) accumulate during packed red blood cell (PRBC) storage. To date, the involvement of EVs in transfusion-related immunomodulation (TRIM) has not been prospectively evaluated in intensive care unit (ICU) patients. This was a prospective subanalysis of a recent observational feasibility study in postoperative ICU patients after: (1) open aortic surgery (Aorta), (2) bilateral lung transplantation (LuTx), and (3) other types of surgery (Comparison). Patient plasma was collected three times each before and after leukoreduced PRBC transfusion at 30-min intervals. The total number of EVs and EVs derived from erythrocytes (EryEVs), total platelets (total PEVs), activated platelets, granulocytes (GEVs), monocytes, and myeloid cells in PRBC samples and patient plasma were analyzed by flow cytometry. Statistical analysis was performed by Spearman's correlation test, linear mixed models and pairwise comparisons by Wilcoxon matched-pairs test. Twenty-three patients (Aorta n = 5, LuTx n = 9, Comparison n = 9) were included in the final analysis. All EV subgroups analyzed were detectable in all PRBCs samples (n = 23), but concentrations did not correlate with storage time. Moreover, all EVs analyzed were detectable in all plasma samples (n = 138), and EV counts were consistent before transfusion. Concentrations of total EVs, EryEVs, total PEVs, and GEVs increased after transfusion compared with baseline in the entire cohort but not in specific study groups. Furthermore, the change in plasma EV counts (total EVs and EryEVs) after transfusion correlated with PRBC storage time in the entire cohort. Extracellular vesicles were detectable in all PRBC and plasma samples. Individual EV subtypes increased after transfusion in the entire cohort, and in part correlated with storage duration. Future clinical studies to investigate the role of EVs in TRIM are warranted and should anticipate a larger sample size.Trial registration: Clinicaltrials.gov: NCT03782623.

Prevalence and long-term implications of preoperative anemia in patients undergoing elective general surgery: a retrospective cohort study at a university hospital.

OBJECTIVE: The aim of this retrospective study was to assess the prevalence of anaemia in a cohort of patients undergoing elective general surgery at a university hospital. Furthermore, the authors investigated the influence of anaemia on short-term and long-term postoperative outcome. BACKGROUND: Awareness of the negative impact of preoperative anaemia on perioperative morbidity and mortality is rising. Anaemia is a potentially modifiable factor, and its therapy might improve patient outcome in elective surgery. Nevertheless, patients with preoperative anaemia frequently undergo elective surgery without receiving adequate preoperative treatment. METHODS: In this single-centre cohort study, the authors analyzed 6908 adult patients who underwent elective general surgery. Patients undergoing day-clinic surgery were excluded. In all patients, preoperative haemoglobin concentration and haematocrit was available. RESULTS: Of all patients analyzed, 32.9% were anaemic (21.0% mild, 11.8% moderate, 1.1% severe). Median time to last follow-up was 5.2 years. During the whole study period, 27.1% of patients died (1.2% died during the hospital stay); median time to death was 1.3 years. Patients with preoperative anaemia had significantly higher mortality rates ( P <0.001) and a higher probability of postoperative complications ( P <0.001). Likewise, receiving blood transfusions was associated with a higher risk of death ( P <0.001). CONCLUSION: This retrospective single-centre analysis confirmed that preoperative anaemia is common, and is a significant risk factor for unfavourable postoperative outcome. As anaemia is a modifiable risk factor, the implementation of a patient blood management concept is crucial to reduce detrimental postoperative events associated with anaemia.

Neurogenetics and Epigenetics of Loneliness.

Loneliness, an established risk factor for both, mental and physical morbidity, is a mounting public health concern. However, the neurobiological mechanisms underlying loneliness-related morbidity are not yet well defined. Here we examined the role of genes and associated DNA risk polymorphic variants that are implicated in loneliness via genetic and epigenetic mechanisms and may thus point to specific therapeutic targets. Searches were conducted on PubMed, Medline, and EMBASE databases using specific Medical Subject Headings terms such as loneliness and genes, neuro- and epigenetics, addiction, affective disorders, alcohol, anti-reward, anxiety, depression, dopamine, cancer, cardiovascular, cognitive, hypodopaminergia, medical, motivation, (neuro)psychopathology, social isolation, and reward deficiency. The narrative literature review yielded recursive collections of scientific and clinical evidence, which were subsequently condensed and summarized in the following key areas: (1) Genetic Antecedents: Exploration of multiple genes mediating reward, stress, immunity and other important vital functions; (2) Genes and Mental Health: Examination of genes linked to personality traits and mental illnesses providing insights into the intricate network of interaction converging on the experience of loneliness; (3) Epigenetic Effects: Inquiry into instances of loneliness and social isolation that are driven by epigenetic methylations associated with negative childhood experiences; and (4) Neural Correlates: Analysis of loneliness-related affective states and cognitions with a focus on hypodopaminergic reward deficiency arising in the context of early life stress, eg, maternal separation, underscoring the importance of parental support early in life. Identification of the individual contributions by various (epi)genetic factors presents opportunities for the creation of innovative preventive, diagnostic, and therapeutic approaches for individuals who cope with persistent feelings of loneliness. The clinical facets and therapeutic prospects associated with the current understanding of loneliness, are discussed emphasizing the relevance of genes and DNA risk polymorphic variants in the context of loneliness-related morbidity.

EPIC Spinal Procedure with Sound Wave Technology Induces Biomechanical Alignment Putatively Influencing Pain Response.

Spinal biomechanical alignment is now able to be altered through the use of unique sound wave technology. This methodological commentary will correlate recent studies demonstrating the ability of sound waves to carry mass, how the EPIC technique spinal procedure uses a sound wave impulse to create measurable changes in spinal alignment, and the clinical safety and efficacy of this approach. The EPIC technique is a direct genealogical descendant of the technique originally developed by the founding family of chiropractic. With sound wave therapies currently being used to break up kidney stones, called lithotripsy, in physical therapy for the treatment of soft tissue injuries, in the treatment of prostate cancer, and in the treatment of Alzheimer's disease, it is possible that the use of sound wave therapies may enter into the realm of altering joint biomechanics. Through a neurovascular examination, the EPIC technique spinal procedure can ascertain the presence of craniocervical subluxation, followed by acquiring multi-dimensional radiographic images for structural analysis. Currently using digital radiographic analysis, the EPIC technique acquires an epigenetic profile of structural asymmetries as well as a multi-directional biomechanical malposition profile of the spine, combining both profiles to ascertain the exact degrees for realignment. EPIC clinics have successfully utilized EPIC on over 20,000 cases. Comparison of pre-treatment biomechanical lateral displacement of the C1 vertebra around the Z-axis measured on digital radiographs, and post-treatment biomechanical lateral displacement of the C1 vertebra measured on digital radiographs immediately following the procedure, demonstrated an average 52% reduction in lateral biomechanical displacement around the Z-axis in a select group of over 2,000 cases. While more research is required, we are encouraged by these preliminary results. WC 265.

"TO BE OR NOT TO BE" GWAS Ends the Controversy about the DRD2 Gene as a Determinant of Reward Deficiency Syndrome (RDS).

Since 1990, there have been thousands of published studies on addiction psychiatry. Several from Blum et al showed the clinical relevance of the Genetic Addiction Risk Severity (GARS) test in identifying risk for reward deficiency behaviors in cohorts from polysubstance abuse and pain clinics, post-surgical bariatrics, and DWI offenders facing prison time. Since Blum et al first published in JAMA (1990) concerning the association of the DRD2 gene polymorphism and severe alcoholism, reactions have been mixed. More recently, however, a meta-analysis of 62 studies showed a significant association between DRD2 rs1800497 and Alcohol Use Disorder (AUD). Other studies from Yale University showed that a haplotype block of the DRD2 gene A1 allele was associated with AUD and heroin dependence. GWAS studies of depression and suicide in 1.2 million veterans confirmed the first psychiatric candidate gene study finding from Blum et al 1990; a significant association between the minor DRD2 allele, Taq A1 and severe alcoholism. Additionally, the DRD2 rs1800497 is robustly associated with suicidal behaviors. Furthermore, DNA polymorphic alleles underlying substance use disorder (SUD) with multiple substances were mapped via chromatin refolding, revealing that the DRD2 gene and associated polymorphism(s) as the top gene signal. Based on these investigations, we conclude that GWAS should end the controversy about the DRD2 gene being one determinant of Reward Deficiency Syndrome (RDS) first reported in 1996.

Longitudinal, prospective study of head impacts in male high school football players.

INTRODUCTION: Repetitive, subconcussive events may adversely affect the brain and cognition during sensitive periods of development. Prevention of neurocognitive consequences of concussion in high school football is therefore an important public health priority. We aimed to identify the player positions and demographic, behavioral, cognitive, and impact characteristics that predict the frequency and acceleration of head impacts in high school football players. METHODS: In this prospective study, three cohorts of adolescent male athletes (N = 53, 28.3% Hispanic) were recruited over three successive seasons in a high school American football program. Demographic and cognitive functioning were assessed at baseline prior to participating in football. Helmet sensors recorded impact frequency and acceleration. Each head impact was captured on film from five different angles. Research staff verified and characterized on-field impacts. Player-level Poisson regressions and year-level and impact-level linear mixed-effect models were used to determine demographic, behavioral, cognitive, and impact characteristics as predictors of impact frequency and acceleration. RESULTS: 4,678 valid impacts were recorded. Impact frequency positively associated with baseline symptoms of hyperactivity-impulsivity [ß(SE) = 1.05 impacts per year per unit of symptom severity (1.00), p = 0.01] and inattentiveness [ß(SE) = 1.003 impacts per year per T-score unit (1.001), p = 0.01]. Compared to quarterbacks, the highest acceleration impacts were sustained by kickers/punters [ß(SE) = 21.5 g's higher (7.1), p = 0.002], kick/punt returners [ß(SE) = 9.3 g's higher (4.4), p = 0.03], and defensive backs [ß(SE) = 4.9 g's higher (2.5), p = 0.05]. Impacts were more frequent in the second [ß(SE) = 33.4 impacts (14.2), p = 0.02)] and third [ß(SE) = 50.9 impacts (20.1), p = 0.01] year of play. Acceleration was highest in top-of-the-head impacts [ß(SE) = 4.4 g's higher (0.8), p<0.001]. CONCLUSION: Including screening questions for Attention-Deficit/Hyperactivity Disorder in pre-participation evaluations can help identify a subset of prospective football players who may be at risk for increased head impacts. Position-specific strategies to modify kickoffs and correct tackling and blocking may also reduce impact burden.

Psychedelics, With a Focus on Psilocybin: Issues for the Clinician.

There has been a burgeoning interest in psychedelics among the public, state legislatures, psychiatrists and other clinical providers, and within the research community. Increasing numbers of studies evaluating psychedelics for depression, anxiety, posttraumatic stress disorder, and substance use disorders have been conducted or are underway. While discussing psychedelics in general, the focus of this paper is on psilocybin and its mechanism, how it exerts a psychedelic effect, dosing, and a review of the treatment studies of psilocybin, which were primarily for treatment-resistant depression and cancer-related anxiety. Future directions and potential limitations of studying and regulating psilocybin and other psychedelics are also discussed.

Prognostic impact of post-treatment FDG PET/CT in anal canal cancer: A prospective study.

BACKGROUND AND PURPOSE: The aim of our prospective study was to assess the prognostic value of 18F-FDG PET/CT performed two months post treatment for anal canal neoplasm. POPULATION AND METHODS: Consecutive patients with histologically proved anal cancer, with 18F-FDG PET/CT pre and two months post treatment were included. Patients were not previously treated for this neoplasm and then received radiotherapy ± chemotherapy. Clinical and pathologic data were collected and for 18F-FDG PET/CT visual and quantitative analysis (standardized uptake value, metabolic volume) were performed; response was classified according to EORTC and PERCIST criteria. The results were assessed for disease free survival and local recurrence free survival using the log-Rank test RESULTS: From December 2014 to September 2019, 94 consecutive patients were screened and 78 were included in this study. Median follow-up was 51 months. Two months post treatment, 37 patients (47.4%) had a complete radiological response according to both EORTC and PERCIST criteria, 66 patients (84.6%) had a clinical complete response. For disease free survival, the prognostic value of complete response was statistically significant (p=0.02) with 18F-FDG PET/CT and with clinical examination (p<0.001). For local recurrence free survival, the prognostic value with 18F-FDG PET/CT was lower (p=0.04) than clinical examination (p < 0.007). CONCLUSION: While clinical examination remains the gold standard for post treatment evaluation in anal cancer, 18F-FDG PET/CT has a statistically significant prognostic value. These two assessments could be combined to improve early evaluation.

Dopaminergic dysfunction: Role for genetic & epigenetic testing in the new psychiatry.

Reward Deficiency Syndrome (RDS), particularly linked to addictive disorders, costs billions of dollars globally and has resulted in over one million deaths in the United States (US). Illicit substance use has been steadily rising and in 2021 approximately 21.9% (61.2 million) of individuals living in the US aged 12 or older had used illicit drugs in the past year. However, only 1.5% (4.1 million) of these individuals had received any substance use treatment. This increase in use and failure to adequately treat or provide treatment to these individuals resulted in 106,699 overdose deaths in 2021 and increased in 2022. This article presents an alternative non-pharmaceutical treatment approach tied to gene-guided therapy, the subject of many decades of research. The cornerstone of this paradigm shift is the brain reward circuitry, brain stem physiology, and neurotransmitter deficits due to the effects of genetic and epigenetic insults on the interrelated cascade of neurotransmission and the net release of dopamine at the Ventral Tegmental Area -Nucleus Accumbens (VTA-NAc) reward site. The Genetic Addiction Risk Severity (GARS) test and pro-dopamine regulator nutraceutical KB220 were combined to induce "dopamine homeostasis" across the brain reward circuitry. This article aims to encourage four future actionable items: 1) the neurophysiologically accurate designation of, for example, "Hyperdopameism /Hyperdopameism" to replace the blaming nomenclature like alcoholism; 2) encouraging continued research into the nature of dysfunctional brainstem neurotransmitters across the brain reward circuitry; 3) early identification of people at risk for all RDS behaviors as a brain check (cognitive testing); 4) induction of dopamine homeostasis using "precision behavioral management" along with the coupling of GARS and precision Kb220 variants; 5) utilization of promising potential treatments include neuromodulating modalities such as Transmagnetic stimulation (TMS) and Deep Brain Stimulation(DBS), which target different areas of the neural circuitry involved in addiction and even neuroimmune agents like N-acetyl-cysteine.

A Swine Model of Neural Circuit Electromagnetic Fields: Effects of Immediate Electromagnetic Field Stimulation on Cortical Injury.

Background Neurologic diseases have profound disability, mortality, and socioeconomic effects worldwide. Treatment of these disorders varies but is largely limited to unique factors associated with neural physiology. Early studies have evaluated alterations in electromagnetic fields (EMF) due to neural disorders with subsequent modulation of EMF as a potential treatment modality. Swine models have begun to be evaluated as translational models in this effect. Methods EMF measurements of a Yucatan miniswine were recorded using proprietary non-contact, non-invasive induction sensors with a dual layer Mu-metal and interlaced copper mesh helmet. The swine then underwent controlled cortical impact (CCI) to simulate traumatic brain injury (TBI). Twenty minutes post-injury after surgical wound closure, the swine underwent targeted EMF signal modulation using a signal generator to stimulate the swine's injured cortical circuit using a sinusoidal wave individualized at 2.5 Hz with a 500mV positive offset at 1V. After 10 days of stimulation, settings were modified to another individualized frequency of 5.5 Hz, 500mV positive offset and 1V for stimulation. Behavioral patterns in swine were evaluated, and EMF measurements were recorded daily prior to, during, and after stimulation. Artificial intelligence (AI) models evaluated patterns in EMF signals. Histology of the stimulated swine cortex was evaluated using hematoxylin and eosin staining and pentachrome staining and compared to a control swine without stimulation and a swine that had received stimulation two days post-injury in a delayed fashion. Serial serum specimens and tissue at the time of euthanasia were obtained for assessment of neuron-specific enolase (NSE) concentration. Results Pre-operative and post-stimulation measurements demonstrated differences in patterns and activity early on. There was an identified peak at 1.6Hz, not frequently seen pre-operatively. There were convergent frequencies in both data sets at 10.5 Hz and 3.9 Hz. Plateaus and decreased variability of changes in slope were identified early in the post-injury phase. AI modeling identified early similarities in pre-operative and post-stimulation measurements through the patterns of peaks with similarities on postoperative day 10 and similarities in the valleys on postoperative day 17. Histologic specimens identified increased degrees of apoptosis and cellular death in the non-stimulated control compared to the stimulated swine. Similarly, the immediately stimulated swine had less apoptosis and increased histologic viability at the site of injury compared to the two-day delayed stimulation swine. There were increased levels of NSE noted in the stimulated swine at the site of injury compared to non-injured sites and the control swine. Conclusions Cortical function was appropriately measured through induction sensors and shielding in the form of a helmet and electromagnetic field channels. Early stimulation resulted in the early and durable recovery of neuronal circuit-driven electromagnetic field patterns. Histology identified increased viability of neurons with fewer apoptotic neurons and glial cells in stimulated swine with early stimulation identifying the best effect compared to a non-stimulated subject. This recovery identifies change and recovery at the circuit, cellular, and subcellular levels that potentiate the need for further study of EMF modulation as a treatment modality in neurological disorders.